Our original compliance hypothesis stated that some of the problems with synthetic small diameter arterial bypass graft patency are related to their lower circumferential compliance, compared to that of the host arteries. Based on theory and circumstantial experimental evidence, large commitments have now been made to the manufacture of a compliant synthetic graft. But our previous studies also suggest that compliance may only be consequential in the presence of a thrombogenic flow surface. The true importance of graft compliance is, therefore, still unclear and is the subject of this proposal. The compliance hypothesis will be tested in dogs by comparing biologic and synthetic arterial grafts of different compliance but identical controlled flow surfaces. The effects of compliance will be examined as those related to the anastomosis alone (anastomotic effects) and to the conduit itself (tubular effects) and each of these will be correlated with the morphology of the tissue-healing response, thrombus deposition and pseudointimal thickening in the graft, calcium and lipid accumulation and endothelial cell coverage. Compliance and its changes with time will be measured using pulsed ultrasound in both animals and man. The interaction of compliance mismatch and other parameters will be studied including a) host artery intimal injury; b) decreased graft wall thrombogenicity; c) more complex anastomotic flow geometry (end-to-side anastomosis); and d) increased platelet reactivity and blood coagulability. Finally, we will study ways of eliminating the anatomotic effects of compliance mismatch and develop improved design criteria for optimum tubular compliance. These studies will lead to an expanded understanding of the mechanism of failures of small vessel grafts and to an improvement in the results with such grafts.